AB0345 THERAPEUTIC DRUG LEVELS TO ACHIEVE GOOD EULAR RESPONSE IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING ADALIMUMAB: RESULTS FROM THE BIOLOGICS IN RHEUMATOID ARTHRITIS GENETICS AND GENOMICS STUDY SYNDICATE (BRAGGSS) COHORT
Authors: R. M. Hum, P. Ho, N. Nair, D. Plant, A. Morgan, J. Isaacs, A. G. Wilson, K. Hyrich, A. Barton
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is a systemic inflammatory disease often treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) such as Adalimumab (ADL), a tumour-necrosis factor inhibitor (TNFi). However, it is known that about a third of patients do not respond to ADL treatment. Previous studies have reported associations between poor response, decreased serum drug levels (SDLs) and poor adherence, but a therapeutic SDL has not been defined nor applied in clinical practice. Objectives To assess median ADL SDLs in RA European Alliance of Associations for Rheumatology (EULAR) good vs non/moderate responders, and to determine cut-off SDLs associated with a “Good” response in fully adherent RA patients. Methods In a prospective observational cohort study, patients with RA were treated with ADL. At baseline, 3-, 6-, and 12-months patients had 4-component DAS28 scores, self-reported treatment adherence data and SDLs measured. Median drug levels and receiver-operator characteristics (ROC) curves were used to compare SDLs between responders and non-responders, and to establish cut-off SDLs in self-reported fully adherent patients. Serum drug levels were measured using a sandwich ELISA produced by Progenika Biopharma. Patients were considered fully adherent if they self-reported never having altered, forgotten or omitted any dose of their biologic drug at follow-up. Between group comparisons were assessed using Fisher’s exact test, with a threshold for significance set at p&lt;0.05. Statistical analyses were performed in R Version 4.1.0 and RStudio Version 1.4.1106. Results A total of 283 RA patients taking ADL were included in the analysis. Baseline characteristics are shown in Table 1. Of these patients 93 (32.9%) self-reported being fully adherent to treatment at 3 months follow-up and had SDLs measured. Table 1. Baseline characteristics of patient cohort with RA taking ADL (n=283) Characteristic n Missing (%) Age at baseline, median years (IQR) 58 (51, 64) 0 Disease duration, median years (IQR) 7 (3, 16) 0 Female Sex, n (%) 206 (73) 0 BMI, median (IQR) 27.4 (23.7, 31.9) 0 Smoking Status 132 (46) Current, n (%) 57 (38) - Ex, n (%) 32 (21) - Non, n (%) 62 (41) - On concurrent DMARD(s) 1 (0.4) No, n (%) 34 (12) - Yes, n (%) 248 (88) - Baseline DAS Score, median (IQR) 5.61 (5.18, 6.14) On MTX at baseline 38 (13) No, n (%) 44 (18) Yes, n (%) 201 (82) In 93 fully adherent RA patients taking ADL at 3 months, good EULAR responders had significantly higher SDLs compared to non/moderate EULAR responders (p=0.0234). In 47/93 (50.5%) fully adherent good responders median SDL at 3 months was 10.94mg/L (IQR 7.75 to 12.0), whereas in 46/93 (49.5%) non/moderate responders, median SDL at 3 months was 9.014 (IQR 6.96 to 11.1). ROC analysis (see Figure 1) reported a 3-month non-trough ADL SDL cut-off of 7.5mg/L in fully adherent RA patients which discriminated Good EULAR responders compared to non/moderate responders with an AUC of 0.63 (95% CI 0.52 – 0.75), 39.1% specificity, and 80.9% sensitivity. Figure 1. ROC curve analysis: EULAR non/moderate vs good responders with 3 month ADL SDLs. Conclusion In keeping with previous work, SDLs were higher in adherent compared with non-adherent patients, but this is the first study to demonstrate that SDLs are higher in fully adherent good EULAR responders compared with non/moderate responders. Based on our methods, cut-offs of 7.5mg/L for ADL may be useful targets in clinical practice to achieve good EULAR response. References [1]Jani M, Chinoy H, Warren RB, Griffiths CEM, Plant D, Fu B, et al. Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis. Arthritis &amp; Rheumatology. 2015;67(8):2011-9. [2]Pouw MF, Krieckaert CL, Nurmohamed MT, van der Kleij D, Aarden L, Rispens T, et al. Key findings towards optimising adalimumab treatment: the concentration-effect curve. Ann Rheum Dis. 2015;74(3):513-8. Disclosure of Interests None declared